The complex nature of the sperm DNA damage process

Esteves, Sandro C.; Agarwal, Ashok; Majzoub, Ahmad

doi:10.21037/tau.2017.05.13

Cited by 17 publications

(13 citation statements)

References 16 publications

(21 reference statements)

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“…During spermiogenesis, histones are replaced by transition proteins and subsequently with protamines ( 104 , 134 ). Cysteine residues of protamines further undergo intra- and intermolecular disulfide cross-linking resulting in a highly condensed chromatin arranged in a toroid ( 116 ). This complex packaging protects the sperm chromatin during its transport from the male to female reproductive tracts and ensures delivery of intact paternal genetic material to the oocyte.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to single- or double-stranded DNA breaks, chromatin damage includes DNA nicks, nuclear protein defects, and alteration of chromatin configuration ( 10 ). Mostly, the tests measure the proportion of sperm with: (I) real DNA breaks (e.g., TUNEL); (II) combination of actual DNA breaks and potentially denaturable DNA due to the preexistence of single-stranded DNA breaks (SS-DB) or double-stranded DNA breaks (DS-DB) (e.g., SCSA, SCD, and Comet); or (III) poor chromatin packaging ( 20 , 104 , 116 ). As noted above, not all types of damage are detected by the same test although SDF test results are interrelated to a greater or lesser extent via properties of the DNA ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…Excessive ROS exert a detrimental effect on male fertility via multiple mechanisms including sperm membrane peroxidation, mitochondrial and nuclear DNA damage, and apoptosis. Redox processes using various pathways, including hydroxyl radical, nitric oxide, and activation of sperm caspases and endonucleases, affect not only the sperm membrane but also nuclear and mitochondrial DNA, thus explaining the higher positivity for SDF in live ejaculated sperm of infertile men than fertile counterparts ( 10 , 116 , 152 ). SDF testing can provide a common pathway to measure the effects of oxidative damage and the success of treatments whether that be varicocele surgery, antioxidants or lifestyle modification ( 153 , 154 ).…”

Section: Discussionmentioning

confidence: 99%

“…In general, the methods for assessing sperm DNA damage can be grouped into three categories, namely: (I) assays that measure DNA fragmentation by incorporating DNA probes or modified nucleotides at the site of breaks; (II) assays that measure both the existing breaks and those generated after DNA denaturation; and (III) assays that indirectly measure the level of chromatin compaction, i.e., nucleus decondensation ( 116 ). While TUNEL belongs to the first group, SCSA, SCD, and Comet are examples of tests from the second group.…”

Section: Discussionmentioning

confidence: 99%

“…Then, a critical analysis of each item listed was carried out using both data from existing literature and relevant supporting information provided by a series of ‘reply to author’ published in TAU journal. The latter ( 82 - 98 ) were ( 99 - 116 ) responses ( 117 - 133 ) provided by the guideline’s authors ( 20 ) to the commentaries ( 24 - 43 ), editorials ( 44 - 62 ), and letters ( 63 - 81 ).…”

Section: Methodsmentioning

confidence: 99%

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A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

Esteves¹,

Agarwal

Cho

et al. 2017

Transl. Androl. Urol.

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BackgroundSperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF.MethodsA search of papers published in response to the CPG entitled “Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios” was performed within the Translational Andrology and Urology (TAU) website (http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as “supportive without reservation”, “supportive with reservation”, “not supportive” or “neutral”. We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the ‘Strengths-Weaknesses-Opportunities-Threats’ (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice.ResultsFifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays’ characteristics. Among ‘not supportive’ and ‘supportive with reservation’ participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility.ConclusionsThe understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pat...

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Section: Discussionmentioning

confidence: 99%